Use of Intraoperative Radioguidance in Recurrent Merkel Carcinoma.

Merkel cell carcinoma is a rapidly progressive nonmelanoma skin cancer with a high risk of recurrence. When recurrence occurs, it is associated with poor prognosis and there is a lack of guidelines for the management of such cases. This article describes a challenging case in which the innovative use of iodine-125 radioactive seeds permitted us to precisely identify and resect two nonpalpable recurrent nodules. The safety and accuracy of the surgical procedure were compromised by the presence of scar tissue following two past resections and two courses of radiotherapy. Radioactive seed localization is a well-known procedure in breast cancer, demonstrating potential for an extended application in other cancer types and in complex clinical situations.

The relevance of preoperative ultrasound cervical mapping in patients with thyroid cancer.

BACKGROUND: Cervical lymph node involvement in thyroid cancer is associated with locoregional recurrence and decreased disease-free survival. Preoperative lymph node mapping helps in planning surgery for neck dissection and improves patient outcomes. We sought to perform a qualitative and quantitative analysis of ultrasound mapping for thyroid cancer and evaluate the clinical importance of this exam in terms of identifying the group of patients who would benefit most from subsequent surgical dissection. METHODS: We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery between 2009 and 2013. We calculated the positive predictive values (PPVs) of ultrasound mapping of both the lateral and central compartments together and the lateral or central compartment individually. A quantitative analysis was performed by comparing the number of positive lymph nodes at ultrasound imaging with histopathologic evaluation. RESULTS: A total of 136 cases of thyroid cancer in 120 patients met the inclusion criteria for ultrasound mapping analysis. The PPVs (and 95% confidence intervals) were 83.82 (0.76-0.89) for the lateral and central compartments, 85.39% (0.76-0.91) for the lateral compartment, and 80.48% (0.7-0.87) for the central compartment. When comparing the positive lymph nodes at ultrasound imaging with histopathologic evaluation, the result was χ(2) = 10.33 (p = 0.006). CONCLUSION: This single-institution study indicated that preoperative ultrasound mapping is an accurate imaging procedure for predicting lymphatic spread in differentiated and medullary thyroid cancer. Ultrasound mapping can be used as an efficient tool for surgical planning and prognosis determination, as well as for identifying the group of patients who would benefit most from subsequent surgical intervention.

CONTEXTE: Dans le contexte du cancer de la thyroïde, l'envahissement des noeuds lymphatiques cervicaux est associé à une récidive locorégionale et à une diminution de la survie sans récidive. Une cartographie préopératoire des noeuds lymphatiques facilite la planification de la dissection du cou et améliore les résultats pour les patients. Nous avons procédé à une analyse qualitative et quantitative de la cartographie par ultrasons dans le contexte du cancer de la thyroïde et avons évalué l'utilité de cette technique sur le plan clinique pour cibler le groupe de patients chez qui une dissection chirurgicale subséquente est indiquée. MÉTHODES: Nous avons évalué rétrospectivement les dossiers de 263 patients ayant subi une thyroïdectomie entre 2009 et 2013. Nous avons calculé la valeur prédictive positive dans le contexte d'une cartographie par ultrasons du compartiment latéral et du compartiment central, conjointement et individuellement. Nous avons ensuite effectué une analyse quantitative en comparant le nombre de noeuds lymphatiques positifs détectés avec la cartographie par ultrasons et l'examen histopathologique. RÉSULTATS: En tout, 136 cas de cancers de la thyroïde, ayant touché 120 patients, respectaient les critères d'inclusion de l'analyse. La valeur prédictive positive était de 83,82 % (0,76­0,89) pour la cartographie conjointe des compartiments latéral et central; de 85,39 % (0,76­0,91) pour le compartiment latéral; et de 80,48 % (0,7­0,87) pour le compartiment central (intervalle de confiance de 95 %). En comparant les résultats de l'imagerie avec ceux de l'examen histopathologique, nous avons obtenu un résultat de χ2 = 10,33 (p = 0,006). CONCLUSION: Menée auprès de patients d'un seul établissement, cette étude a permis de conclure que la cartographie préopératoire par ultrasons est une technique d'imagerie médicale fiable qui permet de prévoir l'envahissement lymphatique chez les patients atteints d'un cancer médullaire ou différencié de la thyroïde. Cette technique peut être utilisée pour planifier une intervention chirurgicale ou établir un pronostic ainsi que pour cibler le groupe de patients chez qui une dissection chirurgicale subséquente serait indiquée.

Sestamibi (99mTc) scan as a single localization modality in primary hyperparathyroidism and factors impacting its accuracy.

BACKGROUND: The proper localization of a hypersecreting parathyroid gland is of vital importance for successful unilateral neck exploration (UNE) and parathyroidectomy. AIM: In this study we aim to evaluate the (99mTc) sestamibi parathyroid scan as a single localizing modality, and we also assess its relation to the weight of the gland and to the preoperative parathyroid hormone (PTH) levels. PATIENTS AND METHODS: We reviewed 170 patients from our hospital (Notre-Dame hospital) from 2005 to 2008, with a mean age of 56.6 years and a female to male ratio of 3.3:1. With primary hyperparathyroidism, all of them had (99mTc) sestamibi parathyroid scan for the localization of the parathyroid adenoma. Preoperative and postoperative PTH levels were recorded. The histopathology reports confirmed the diagnosis and weight of the diseased gland, which were recorded every time. The results were analyzed and correlated with the sestamibi results, to evaluate its accuracy. RESULTS: Seventy-eight patients (41%) of the 170 had an exact match (EM) sestamibi results, 81 (51.6%) had a partial match, and only 11 patients were reported as mismatch. Analyzing the mean weight of the gland in each group between matching (EM, PM) versus mismatch resulted in a mean difference of 0.823 g (1.05 and 0.247 g, respectively) P = 0.045. Hyperplasia to adenoma ratio was more in the partial matching group (18.5%) versus the exact matching group (7.6%). Finally the mean PTH level was higher in the EM group (28.8 pmol/L) compared to the mismatch group (10.1 pmol/L) P = 0.02. Overall sensitivity and specificity for the (99 mTc) sestamibi in our data was 98.1 and 97%, respectively. CONCLUSION: (99mTc) sestamibi is a highly accurate test that can be employed as a single localizing modality for identifying a hypersecreting parathyroid, a UNE, or a parathyroidectomy. The weight of the gland plays an important role in the accuracy of the test, as also the preoperative PTH levels.

Delayed serum calcium biochemical response to successful parathyroidectomy in primary hyperparathyroidism.

BACKGROUND: Parathyroidectomy is considered the standard treatment for primary hyperparathyroidism, however, though the onset of biochemical response is variable and is different from one patient to the other. AIM: To evaluate the onset of systemic response and the biochemical normalization of serum calcium levels to a successful surgery. PATIENTS AND METHODS: In a retrospective fashion, we collected clinical data from 303 patients admitted to our hospital between 2005 and 2008, with a diagnosis of primary hyperparathyroidism after sestamibi localization. The pathology reports, parathyroidectomy results, the preoperative and postoperative parathormone (PTH) and serum calcium levels were reviewed. Response of each patient to the surgery was studied and all the data were analyzed to determine how fast the serum calcium levels drop. RESULTS: The majority of patients (72.9%, 221/303) showed a decrease in their serum calcium levels to normal values within 48 h. While in 40 patients it took 72 hours and 42 patients (13.8%) had a delayed normalization for more than 72 h. The pathology in the PH group was predominantly of a single adenoma 80.9% vs.19.1 with hyperplasia with a P of 0.03. Preoperative parathyroid hormone PTH elevation was not significantly deferent between the two groups (PH and EN) with a mean of 7.9±5.36 vs. 7.41±14.5 pmol/L respectively with a P of 0.43. CONCLUSION: The majority of patients with primary hyperparathyroidism (PHP) respond to parathyroidectomy in the form of normalization of their serum calcium levels and PTH within 48 h; however, a certain group of patients will need more than 3 days.

Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism.

BACKGROUND: Non-(1-84) parathyroid hormone (PTH) fragments are large circulating carboxyl-terminal (C) fragments with a partially preserved amino-terminal (N) structure. hPTH (7-84), a synthetic surrogate, has been demonstrated to exert biologic effects in vivo and in vitro which are opposite to those of hPTH (1-34) on the PTH/PTHrP type I receptor through a C-PTH receptor. We wanted to determine the N structure of non-(1-84) PTH fragments. METHODS: Parathyroid cells isolated from glands obtained at surgery from three patients with primary hyperparathyroidism and three patients with secondary hyperparathyroidism were incubated with 35S-methionine to internally label their secretion products. Incubations were performed for 8 hours at the patient-ionized calcium concentration and in the presence of various protease inhibitors. The supernatant was fractionated by high-performance liquid chromatography (HPLC) and fractions were analyzed with PTH assays having (1 to 4) and (12 to 23) epitopes, respectively. The serum of each patient was similarly analyzed. Peaks of immunoreactivity identified were submitted to sequence analysis to recover the 35S-methionine residues in positions 8 and 18. RESULTS: Three regions of interest were identified with PTH assays. They corresponded to non-(1-84) PTH fragments (further divided in regions 3 and 4), a peak of N-PTH migrating in front of hPTH (1-84) (region 2) and a peak of immunoreactivity corresponding to the elution position of hPTH (1-84) (region 1). The last corresponded to a single sequence starting at position 1. Region 2 gave similar results in all cases (a major signal starting at position 1) but also sometimes minor sequences starting at position 4 or 7. Regions 3 and 4 always identified a major sequence starting at positions 7 and minor sequences starting at positions 8, 10, and 15. Surprisingly, a major signal starting at position 1 was also present in region 3. The HPLC profile obtained from a given patient's parathyroid cells was qualitatively similar to the one obtained with his/her serum in each case. CONCLUSION: These results indicate that non-(1-84) PTH fragments are composed of a family of fragments which may be generated by specific or progressive cleavage at the N region. The longest fragment starts at position 4 and the shortest at position 15. A peptide starting at position 7 appears as the major component of non-(1-84) PTH fragments. The generation process is similar to the one described for smaller C-PTH fragments a number of years ago, suggesting a similar production mechanism and source for all C-PTH fragments.

Overproduction of an amino-terminal form of PTH distinct from human PTH(1-84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery.

OBJECTIVE: Rare patients with severe primary hyperparathyroidism present with large parathyroid tumours, severe hypercalcaemia, very high PTH levels and osteitis fibrosa cystica. Some of these patients display a large amount of C-PTH fragments in circulation and present with a higher C-PTH/I-PTH ratio than seen in less severe cases of primary hyperparathyroidism. We wanted to determine how PTH levels and circulating PTH high-performance liquid chromatography (HPLC) profiles analysed with PTH assays having different epitopes could be affected by medical and surgical treatment in such patients. DESIGN: A 55-year-old man with severe hypercalcaemia (Ca(2+): 2.01 mmol/l), very high PTH levels (CA-PTH 82.1 and T-PTH 72 pmol/l) caused by a large parathyroid tumour (7.35 g) and accompanied by significant bone involvement (alkaline phosphatase of 185 UI/l and subperiostal bone resorption of hands) was referred to us. Blood was obtained at various time points during his medical treatment, before and after surgery, to measure parameters of calcium and phosphorus metabolism, and of bone turnover. HPLC separations of circulating PTH molecular forms were performed and analysed with PTH assays having 1-4 (CA), 12-18 (T), 26-32 (E) and 65-84 (C) epitopes. RESULTS: Before surgery, serum Ca2+ was nearly normalized with hydratation, intravenous (IV) pamidronate and oral vitamin D administration. Despite a decrease in Ca2+ to 1.31 mmol/l, CA-PTH and T-PTH levels decreased by half in relation to a threefold increase in basal 1,25-dihydroxyvitamin D [1,25(OH)2D] level (94 to 337 pmol/l). After this initial positive response, hypercalcaemia and elevated CA- and T-PTH levels recurred even if 1,25(OH)2D levels remained elevated. The tumour was removed surgically and proved to be poorly differentiated with nuclear atypia and mitosis. After surgery, the Ca2+ level and PTH secretion normalized. The higher CA-PTH level relative to the T-PTH level observed before surgery in this patient was related to the oversecretion of an amino-terminal (N) form of PTH recognized by PTH assays with (1-4) or (26-32) epitopes but not by the T-PTH assay with a (12-18) epitope. This molecular form represented 50% of CA-PTH measured in this patient, but only 7% in less severe cases of primary hyperparathyroidism. It was unaffected by medical therapy and disappeared after surgery. CONCLUSION: The relationship between the overexpression of this N-PTH molecular form and severe primary hyperparathyroidism remains unclear. Further studies will be required in these rare patients to see whether N-PTH is a marker of less well differentiated parathyroid tumours and/or relates to the overproduction of C-PTH fragments in the presence of severe hypercalcaemia.

Cisatracurium pharmacodynamics in patients with oculopharyngeal muscular dystrophy.

The pharmacodynamics of muscle relaxants in patients with oculopharyngeal muscular dystrophy (OPMD) have never been studied. We designed this study to compare the pharmacodynamics of cisatracurium in OPMD patients versus a control group. Forty patients were enrolled: 20 OPMD patients requiring general anesthesia for cricopharyngeal myotomy and 20 age-matched controls undergoing an operation of similar duration and expected blood loss. Anesthesia was standardized, and both groups received a bolus of cisatracurium 0.1 mg/kg. Onset time, time to 10% T1 recovery, and the intervals 10%-25% and 25%-75% were calculated for both groups. A subgroup analysis was performed in patients with a more severe form of OPMD. Demographic and intraoperative data were similar. Onset time was significantly longer in OPMD patients compared with the control group (4.6 +/- 1.5 min versus 3.4 +/- 1.0 min; P = 0.001). There was no difference in recovery times or indices between groups, regardless of the severity of the disease. In conclusion, there was no difference in the duration of a cisatracurium-induced neuromuscular block between OPMD patients and a control group. A delayed onset of action of the drug may occur.

International prospective evaluation of scintimammography with (99m)technetium sestamibi.

BACKGROUND: The purpose of this study is to evaluate the efficacy of scintimammography with (99m)Technetium-Sestamibi for the diagnosis of breast cancer. METHODS: This was a multicenter prospective cohort clinical trial. A total of 1,734 women were enrolled of whom 1,243 had complete data upon study completion. RESULTS: The mean +/- standard error age of the patients is 56 +/-12 years (with a range of 19 to 94). Mammographic results were classified by the Breast Imaging Reporting and Data System (BIRADS) as 199 (16%) BIRADS 5, 149 (12%) BIRADS 4, 199 (16%) BIRADS 3, and 696 (56%) BIRADS 2 or 1. Scintimammography was positive for 322 (26%) of the patients and negative for 921 (76%). Histopathology showed malignancy for 201 (16%) of the patients. Sensitivity and specificity of scintimammography was estimated 93% and 87% respectively. A positive predictive value (PPV) of 58% with a negative predictive value of 98% were calculated. CONCLUSIONS: The present study suggests that scintimammography with (99m)Technetium-Sestamibi is highly accurate for the detection of breast cancer.

Maternal preoccupation and parenting as predictors of emotional and behavioral problems in children of women with breast cancer.

PURPOSE: To test the hypothesis that differences between sicker and not-so-sick women in their preoccupation with their illness and parenting behavior can explain why some investigators find that children of breast cancer patients fare better than controls and other investigators find the reverse. PATIENTS AND METHODS: Forty-two women with metastasized breast cancer (sicker mothers) and 45 women with a first occurrence of nonmetastasized breast cancer (not-so-sick mothers) rated the degree of their preoccupation with the disease, their parenting behavior, mood, and social supports and the emotional and behavioral symptoms in one of their children. Their 12- to 18-year-old children rated their mothers' parenting behavior, their own emotional and behavioral symptoms, and their self-esteem. RESULTS: Sicker mothers reported relatively less preoccupation. They, and their children, reported less poor parenting and fewer externalizing symptoms in the children. Regression analyses revealed further differences between the groups. CONCLUSION: Less preoccupation with their illness and less poor parenting behavior by sicker mothers may explain why their children seem to fare better then those of not-so-sick mothers. Formulations concerning families of breast cancer patients should include consideration of the effect of the mothers' perception of the severity of their illness.